A new prognostic model to predict renal outcome in autosomal dominant polycystic kidney disease (ADPKD). E. Cornec-Le Gall1-4, MP. Audrézet2-4, M. Hourmant5, MP. Morin6, C. Charasse7, E. Renaudineau8, B. Wehbe10, P. Jousset11, MP. Guillodo12, N. Terki13, S. Benarbia14, R. Perrichot16, T. Sawadogo9, S. Régnier-Le Coz15, C. Savoiu17, Y. le Meur1-2, C. Ferec2-4, 18, the Genkyst Study Group 1) Department of Nephrology, Centre Hospitalier Universitaire de Brest; 2) Université Occidentale de Bretagne; 3) INSERM U1078; 4) Department of Molecular Genetics, Epidemiologic Genetic and Histocompatibility, Centre Hospitalier Universitaire de Brest; 5) Department of Nephrology, Centre Hospitalier Universitaire de Nantes; 6) Department of Nephrology, Centre Hospitalier Universitaire de Rennes; 7) Department of Nephrology, Centre Hospitalier de Saint Brieuc; 8) Department of Nephrology, Centre Hospitalier de Saint Malo; 9) Department of Nephrology, Centre Hospitalier de Lorient; 10) Department of Nephrology, Centre Hospitalier de Quimper; 11) Department of Nephrology, Centre Hospitalier de Pontivy; 12) Centre de Dialyse, Association des urémiques de Bretagne, Brest; 13) Société Brestoise du Rein Artificiel, Brest; 14) Centre de Dialyse, Association des urémiques de Bretagne, Quimper; 15) Department of Nephrology, Centre Hospitalier de Saint Nazaire; 16) Department of Nephrology, Centre Hospitalier de Vannes; 17) Centre associatif de Dialyse, ECHO, Nantes; 18) Etablissement Français du Sang, Brest.

   ADPKD is marked by a high clinical variability, especially in regards of age at end-stage renal disease (ESRD). As we are shifting to the era of targeted therapies in ADPKD, one needs to target the patients who are more likely to develop ESRD and thus to benefit from those therapies. In that setting, we conducted a cross-sectional study in a population of 1130 patients (525 males) from all the nephrology centers (n=17) of a single area, Brittany, France. We evaluated the effect of 10 clinical variables and of the molecular genetic data (mutation of PKD2, non truncating mutation (NTM) of PKD1 or truncating mutation (TM) of PKD1) using Kaplan-Meier curves and univariate followed by multivariate Cox regression analyses and built a score weighting each significant factor according to the HR obtained. Internal validation was assessed using non parametric bootstrapping with replacement. Discrimination of the model was evaluated using the c-statistic, which represents area under time-dependant ROC curves. Median age at inclusion was 54.3 yrs [5.45-94.3]. After multivariate analysis, 4 factors remained significantly associated with renal survival : Gender (HR=1.55, 0.95 CI=1.25-2.93), Hypertension onset before age 35 (HR=2.24, 0.95 CI=1.76-2.86), first urological complication before age 35 (at least 1 amongst gross hematuria, flank pains related to cysts or cyst infection) (HR=2.1, 0.95 CI=1.62-2.73), and genetic status (PKD2 vs NTM of PKD1 HR=1.93, 0.95CI=1.27-2.93, vs TM of PKD1 HR=4.88 0.95CI=3.39-7.02). We thus defined a score ranging from 0 to 9 (male gender:1 pt, hypertension onset before age 35: 2 pts, first urological complication before age 35: 2 pts, PKD2 mutation: 0 pt, NTM of PKD1: 2 pts and TM of PKD1: 4 pts). The accuracy of the PRO-PKD score applied to the sample was high, with a c-statistic of 0.863 at 65 yrs. To facilitate ease-of-use, we defined 3 risk categories: low risk, intermediate and High-Risk of early progression to ESRD with median ages at ESRD of respectively 73.6, 57.7 and 48.5 yrs (HR: Intermediate Risk=3.99, High-Risk=13). Predicted probabilities of ESRD at age 60 were 16.5%, 57.5%, and 91.2%; for the Low, Intermediate, and High Risk Group, and accorded well with observed ESRD frequencies. The PRO-PKD score is a simple, accurate and easy-to-use prognostic score that might be of interest in the selection of the patients who should be included in the ADPKD clinical trials and be a valuable tool for personalized medicine in ADPKD.

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